Fluorinated benzyl alcohols are not only important intermediates for the preparation of pharmaceuticals and crop protection agents (WO 95/19 980, DE-A 2,714,042) but also have a schistosomacidal action (U.S. Pat. No. 3,855,291) and are used as components in microbicides (DE-A-233,849, U.S. Pat. No.4,167,583).
It is known from EP-B 265,854 that fluorobenzaldehydes can be prepared from chlorobenzaldehydes using alkali metal fluorides in a dipolar aprotic solvent. The yield is 68% of theory, which is unsatisfactory.
In addition, the weight ratio of starting material to solvent is 1:5.7, resulting in a poor space-time yield.
EP-B 523,668 describes the preparation of difluorobenzaldehydes from dichlorobenzaldehydes by reaction with alkali metal fluorides in a dipolar aprotic solvent in the presence of ethylene glycol dialkyl ethers as catalyst. The catalyst is used in amounts of from 10 to 50 g per mol of dichlorobenzaldehyde. Even in the unpurified product, the yield of difluorobenzaldehydes is always less than 75%. The solvent is used in an amount of 400 g per mol of dichlorobenzaldehyde, which corresponds to 2.5 mol of dichlorobenzaldehyde per kg of solvent. A disadvantage is the large amounts of catalyst and solvent which are employed to achieve only an unsatisfactory yield.
According to EP-B 289,942, fluorobenzaldehydes are prepared by reacting chlorobenzaldehydes with metal fluorides in bulk or in aromatic hydrocarbons in the presence of quaternary phosphonium salts and/or quaternary ammonium salts and, if desired, further catalysts. The catalysts are used in amounts of from 5 to 50 mol %, based on the chlorobenzaldehyde. The yields are in the range from 41 to 75% but only reach values above 55% when a mixture of two different types of catalyst is used. Even then, the yields are still unsatisfactory.
The previously described processes of the prior art for preparing fluorinated benzaldehydes all require high temperatures and give products containing by-products which can be removed only with great difficulty. Both are disadvantages, high temperatures because they require a lot of energy and by-products which are difficult to remove because they cannot be tolerated in intermediates for active compounds. If the temperature is lowered, e.g., in the process of DE-A 3,637,156, the yield also drops drastically even when longer reaction times are employed (see Comparative Example).
It is also known that fluorinated benzyl alcohols can be obtained from the corresponding benzoic acids by reduction with lithium aluminum hydride or from the corresponding benzoyl chlorides by reduction with alkali metal boranates. The starting materials used here are fluorine-substituted acid chlorides in which the fluorine has been introduced via a halogen replacement reaction or aminobenzoic acids which have been converted into fluorine-substituted derivatives by diazotization in hydrogen fluoride or by the method of Balz-Schiemann (see Houben-Weyl, Methoden der organischen Chemie, 4th edition, volume 5/3, pages 215 and 227). All these processes require the use of metal hydride reagents in the reduction to the benzyl alcohol and therefore can be carried out in industry only with difficulty. In addition, they are expensive.
A further source of fluorinated benzyl alcohols is the corresponding benzyl chlorides or bromides which can be obtained by side-chain halogenation of the corresponding fluorinated toluenes. However, these toluenes are frequently difficult to obtain or can only be prepared from the products which are of interest here.
DE-A 2,333,849 discloses that 2,4-difluorobenzaldehyde can be converted into 2,4-difluorobenzyl alcohol in a yield of 68.6% by hydrogenation over Raney nickel. Disadvantages of this process are not only the large amount of catalyst (31 g per mol) and the large amount of a solvent (1100 ml per mole) but also the unsatisfactory yield of 68.6%. These factors result in an unsatisfactory space-time yield. The aldehyde used was obtained here from the difficult-to-obtain 2,4-difluorotoluene by side-chain chlorination and subsequent hydrolysis.
In summary, it can be said of the prior art that there has hitherto been no satisfactory process for preparing fluorinated benzaldehydes from chlorinated benzaldehydes, since this reaction has hitherto been able to be carried out only at unsatisfactory yields and does not give the desired products in the required purity, even when it is carried out in dilute medium or using two catalysts, and that the preparation of fluorinated benzyl alcohols by reduction has hitherto either required difficult-to-handle and expensive reducing agents or has started from difficult-to-obtain starting materials or, in the case of the reduction of corresponding aldehydes with hydrogen in the presence of Raney nickel, has given only moderate yields. The yields and purities of the products obtainable by the known methods do not satisfy, in particular, the requirements for the synthesis of active compounds.